Download Why Herb Products Rather Than Single Compounds?

fall Winter book 05
1/2/05
2:16 pm
Page 29
HISTORY & PHILOSOPHY
29
Why Herb Products Rather Than
Single Compounds?
by Francis Brinker, ND
Using plants as agents for health is as old as life on this
The preference in natural products pharmacy and
earth. The art of their application has been refined
medicine for purified compounds allows scientists more
through the ages, but the affinity of humans for plants has
control over the manufactured consistency and precise
formed beneficial relationships that exist on many levels.
quantification of the content of pharmaceutical products.
Not the least of these involves vitality and healing. Almost
Given these advantages, why would the use of a complex
a century ago, John Uri Lloyd, innovative Eclectic
medicinal herb be preferred over its most active
pharmacist from 1871 to 1936, expressed it simply:
component? Changes in absorption, metabolism, and
excretion are manifested in both the effects and toxicity
“Listen, man of science, listen to the words of
when the complexity is removed from botanical products.
wisdom, spoken once but yet lastingly and forever to
The types of changes and potential outcomes are many
all mankind… Among the earliest remedial agents …
and depend on the extent of the alterations made in the
Francis Brinker has
are plant products and plant educts. … The most
herb as it is used whole or extracted, fractionated, and
taught botanical
conspicuous of all remedies, as well as foods, have
concentrated. Lloyd described the rationale of whole plant
medicine at both
been those formulated under the influence of
use to his fellow pharmacists:
National College of
Naturopathic Medicine
vegetable life. The “simples” of the aborigines … the
and Southwest College
remedies of domestic medicine … the agents that
“Among the earliest remedial agents, as well as the
science most values and most studies, have been and
most useful remedies of the present, are plant
yet are, plant structures. The one great bank of wealth
products and plant agents. … No balanced mind,
teaches in Dr. Andrew
that conserves life is the green bank of vegetation that
informed concerning the record of remedial agents of
Weil’s Program in
encircles the globe. … The cherished remedies have
the past, and their qualities at present, will deny the
Integrative Medicine at
they been of all nations. No more are they to be
supremacy of vegetable structures as corrective agents
the University of
displaced by any artificial substitute than are
in the hands of men qualified to use them
Arizona.
vegetable foods to be replaced by synthetics evolved
intelligently. The life of man and the health of man
Dr. Brinker has written
by the chemist. …Nor will a person, if he thinks,
depend on the conservation of energy held in the life
numerous articles and
under-value the inorganics in vegetable medicines,
forces that are locked in vegetable structures, be they
books on medicinal
where either alone, or as integral parts of plant
called food or remedy. … They produce changes in
herbs, including The
structures they do well their part. … No balanced
organs or in structures by their influence on nerve
mind, informed concerning the records of the
current or on vitalized matter. They are natural plant
remedial agents of the past, or their qualities as
structures, which experience has taught, as a crude
known at present, will deny the supremacy of
whole, can influence or conserve life structures.
vegetable structures as food products or as corrective
…The proportions and relationships of the
agents, in the hands of men qualified to use them
intercellular structures of certain parts of the plants
intelligently.” (Lloyd 1909a)
used in medicine vary. … And so empiricism or
of Naturopathic
Medicine and currently
Eclectic Dispensatory of
Botanical Therapeutics,
Herb Contraindications
and Drug Interactions,
and The Toxicology of
Botanical Medicine.
observation led to the first attempt to make more
Fall/Winter 2004 Journal of the American Herbalists Guild
J A H G
fall Winter book 05
1/2/05
2:16 pm
Page 30
© Courtesy of the Lloyd Library and Museum. Special Collection 106, Box 1.
30
“Rebel in the Laboratory,” a photograph of John Uri Lloyd.
J A H G
uniform preparations from the crude parts used in
qualities are they established in pharmacy and
medicine. … These energetic chemically-constructed
therapy, but a blank are they to the chemist’s art.
ultimates seemed to indicate that behind every
…Unquestionable evidence taught that fragments
natural remedy lay a definite something that could
created out of drugs by chemistry do not parallel the
replace in therapy the parent structure. … That it
natural intermolecular structures that establish drugs
was a natural line for enthusiasm to take is apparently
as remedies…Much of the present discouragement of
supported by the aggressive energies of a few educts
Regular physicians is surely due to the use of
and products, such as … the energetic alkaloids, and
fragments only. Unwisely they have ignored the
a few other products which possess in themselves
claims of plant structures which in themselves are
qualities to remind one of the parent structures. …
valuable in medicine, but are neglected and discarded
We observe that medical nihilism, too often the
because the test tube and reagent of the chemist
result of such medication, is fostered by continued
cannot create from them bodies like unto the
disappointment in directions where structures, not
poisonous alkaloids, atropine, strychnine, morphine.
fragments, dominate a drug [dried herb]. The great
These men seek the hurricane; the still, small voice
mass of organic remedial agents has no one
has no part in such medication….Eclectic thought
dominating definite structure capable of either
comprehended the situation in the latter part of the
isolation or of yielding, by chemical destruction,
last
definite ultimates. … In the materia medica of
experimentation came into possession of a great, rich
intercellular structures, no one chemically-made
field which the Regular physician had unwittingly
fragment that can be broken out parallels the drug as
relinquished. It turned toward the evolution of a
a whole, if one knows the whole drug. … Inter-
standard form of clean remedies, as nearly devoid of
structural compounds exist, by their well-known
common plant dirt as possible, which should parallel
Journal of the American Herbalists Guild Fall/Winter 2004
[19th]
century,
and
through
clinical
fall Winter book 05
1/2/05
2:16 pm
Page 31
the natural drugs as a whole, not be a fragment only.
Drugs. – The evolution of drugs presents some very
… The one school in American medicine that has
curious paradoxes. For example, a drug may be
given its thought, its culture, its aim in the treatment
introduced originally as a remedy to be used in a
of disease by structural vegetable remedies is
certain ailment. As time passes, this use may be
acknowledged to be the Eclectic school. …
discontinued, the drug slipping gradually into quite
Textbooks, materia medicas, works on practice,
another field of service. This, however, does not
descriptive both of the drugs and their action in
necessarily establish its lack of value in its original
disease, were written. … The evolution of these
field. … The act of manipulation destroys, creates,
Eclectic remedies has been clinical, experimental in
and recreates, to the third and fourth generation. Nor
human disease expressions (not on animals in
is this due alone to the heat employed in the
health), by a rule which necessitated a long and
manipulation. … Temperature, time influences, have
circumspect study of each remedy. … Due credit is
their play of changes, in the face of the manipulator.
given isolated substances in their useful places.
He begins with a drug that is a mass of structural
Indeed, the credit of discovering those most valued in
uncertainties. He ends with a mass of uncertainties
American plant life is to be credited to Eclecticism.
that did, or did not, exist originally. …Macrotys. –
But we value above all the interstructural effect that
The drug Macrotys (Cimicifuga) is an apt example of
comes from life-bound structures endowed with their
the failure of heroic chemistry to parallel natural
full vital qualities, preserved in assimilable form.”
constituents with an ultimate. … The bulk of the
(Lloyd 1905)
“resin” (so called) of Macrotys is not a resin, nor is it
HISTORY & PHILOSOPHY
31
a complexity that exists in the drug. It is a compound
Lloyd was no stranger to isolates. He earned his third
of unknowables, by reason of the fact that the
Ebert Prize for distinguished research in pharmacy by
complex mixture of its bodies is split into by-
developing Lloyd’s Reagent, known under the trade name
products by action of air and drying, some of these
Alcresta, for the purpose of separating alkaloids from
being soluble in water, others insoluble. These
solutions. Licensed to Eli Lilly & Co., Lloyd’s
changes begin when the drug starts to dry. They
development of an atropine sulfate preparation from
continue under atmospheric influence and moisture
Datura led to its manufacture by Lilly to supply the U.S.
to practical infinity…Perhaps no more typical
military during World War I for treatment of eye wounds.
example could be mentioned than this drug
He was quite cognizant of the differences between this
Macrotys (Cimicifuga) of the gradual change of its
alkaloid and the plants from which it is derived and other
similar derivatives.
“Separates Do Not Represent the Drug. – … Consider
Belladonna, which yields atropine, but yet does not in
nature contain it. The process of manipulation
produces atropine from Belladonna, but the natural
alkaloid atropine exists in the drug Hyoscyamus.
action from Belladonna, it is a question as to the
textural setting of the alkaloidal structure. In
addition, there are associated structures that need be
considered as influencing partners of every natural
drug. This writer ventures to disagree with the view
Courtesy of David Winston
However, since Hyoscyamus differs greatly in its
that Atropine parallels Belladonna, or that
Hyoscyamine parallels Hyoscyamus, or that either
Label from Specific Echinacea bottle by Lloyd Brothers.
drug parallets the other, as a whole….Evolution of
Fall/Winter 2004 Journal of the American Herbalists Guild
J A H G
fall Winter book 05
1/2/05
2:16 pm
Page 32
32
field of action as employed by physicians. Heralded
medicine. Probably the most pronounced objection
in 1832 as a great remedy for smallpox, it was revived
to the use of this drug is the intense bitterness of the
in 1872 as “superior to vaccination.” In 1848, Dr.
preparations. … The action of the drug in overdoses
N.S. Davis of Chicago considered Macrotys to be
is distressing, although in Eclectic doses no toxic
“the most purely sedative agent we possess.”” (Lloyd
trouble is experienced. … Mr. Charles W. Moore,
1932b)
under the auspices of Professor Frederick B. Power, of
the Wellcome Chemical Research Laboratories,
In his struggles to achieve a practical solution to the
shows that from apocynum can be obtained a poison,
quandary of living plants and their medicinal chemistry,
and that this poisonous substance is capable of killing
Lloyd determined that separating out the so-called active
dogs in a very short time. This fact will be sufficient,
principles did not provide an adequate representation of
we take it, to introduce the drug to those who seek
the action of the fresh plant:
poisonous drug effects, or some toxic preparation
made from it, authoritatively as a remedy. … And
The traditional
preference for the
“I would not in this place, … leaving plant crudities,
now as to one of our reasons for believing that this
more than refer to those substances that are accepted
investigation (made in England) will establish
complexity of
to be proximate plant constituents, and of which the
apocynum as a remedy in this country, in a direction
herbs and their
dead alkaloids seem now to be unfolding into an
where a sevety-five years’ use of the drug by
native extracts
orderly unity, and to be yielding a system. These
physicians who have employed it in disease
several plant principles are evolved from defunct
expressions, and know how to apply it in disease, has
plants by methods of pharmacy and chemistry. They
failed to make an impression….Listen! When the
repeated clinical
appear from the nether side of phytivorous
ethyl acetate and the alcohol extract from Resin A
experiences.
demolition, and there is a trackless space between the
were administered per os to dogs, in doses of five and
living plant and these sapless, disarranged products.”
a half grains [357 mg], the dogs were killed. … One
(Lloyd 1922)
and a half grain [97 mg] apocynamarin, per os,
was based on
violently vomited the dogs. … We make the
The established therapeutic uses of plants or empirical
prediction that after a physiological crusade, in which
understanding of the adverse effects does not satisfy the
its toxicity is thoroughly established (but not that this
scientifically-minded until a tentative “active ingredient”
is the reason for its therapeutic value) there will be no
and “mechanism of action” has been proposed and
addition whatever made in its present Eclectic
explained. However, this level of understanding is
therapeutical applications. … Let it not be forgotten
insufficient to grasp the therapeutic implications of the
that the common name of this drug, dog’s bane,
combined components and their activities known from
indicates the fact that even the common people in
clinical applications of complex plant products.
the
Nonetheless, the conventional medical belief remains that
experimentation on dogs to teach them that
identifying isolated effects of specific components,
apocynum, dog’s bane, will kill dogs.” (Lloyd 1909b)
century
past
needed
no
physiological
however limited or direct their actual contribution to its
total usefulness or risks, is necessary to establish the
The reluctance to believe that the value of botanical
validity of a remedy. Though a distinguished analyst of
remedies can be reduced to a single active compound that
plant components himself, Lloyd was dismayed by the
is representative of its medicinal effects was not peculiar to
binding limitations of this narrow perspective:
Lloyd but was commonly shared by many in the medical
profession of his day. The isolated component stood at
J A H G
“Apocynum…as is well known, is one of the standard
one extreme of medicinal choices, while botanicals and
old Eclectic remedies. It is used in confidence by
their extracts remained as the preferred conventional
physicians who know how to employ it, and it is
means of medication. This preference is illustrated by an
considered invaluable by recognized authorities, who
editorial in the New York Medical Journal. It insists that
have a life-time’s experience in the practice of
isolated compounds should not become the sole means of
Journal of the American Herbalists Guild Fall/Winter 2004
fall Winter book 05
1/2/05
2:16 pm
Page 33
HISTORY & PHILOSOPHY
33
administering medications.
“The time is yet far distant when we can depend
upon active principles alone for the curative
treatment of disease. The complex of constituents
represented by the whole drug substance or a tincture
or extract of it cannot be dispensed with. … This
latter day tendency to administer attenuated doses of
the alkaloids and alkaloidal principles, glucosides,
etc., is in a measure to be depolored. It is important,
of course, to employ definiteness of dose with the
sure knowledge of effect, but, at the risk of being
classed among the empiricists, we must confess to a
feeling in favor administering the whole drug, either
in the form of powder, extract, or tincture.”
(Anonymous 1910)
The traditional preference for the complexity of herbs and
their native extracts was based on repeated clinical
experiences. Desirable outcomes achieved by using less
concentrated products are also less likely to induce an
adverse imbalance from their multifaceted influence. It is
here that a word may aptly be said about the concept of
synergism. The term ‘synergistic’ is applied to the
combined actions of a number of botanical constituents as
they affect the same pathological process or condition
through different mechanisms. The therapeutic outcome
are added together. (The whole is greater than the sum of
its parts.)
A recent study illustrated the advantage of synergism
in complex extracts of the Himalayan plant daruharidra
© Martin Wall
expected if the effects of each known active component
Courtesy of David Winston
of the combined actions can be greater than would be
compared to fractions and a major isolated constituent
(Bhandari et al 2000). Powdered bark was decocted in
Advertisement for Lloyd Brothers Echinacea
water, typical of its traditional Ayurvedic use. This extract
was also separated into two fractions containing either 7
quaternary alkaloids (including berberine) or 5 non-
species. Its quaternary alkaloids were as potent for 11, less
quaternary alkaloids. Another extract of the bark was
so for 1, and more so for 8 species, as were its non-
made by cold infusion in methanol. The activity of the
quaternary alkaloids for 12, 3, and 5 species, respectively.
two native extracts and two fractions against 19 species of
The methanol extract was as good as berberine against 6,
bacteria plus Candida yeast in test tubes were compared to
less than for 1, and better against 13 species.
those of the “main” antiseptic alkaloid, berberine, based
Bhandari and colleagues further demonstrated using
upon the minimal inhibitory concentrations (MIC). In
the MIC that methanol extract was (or tied) the most
relation to berberine, the aqueous extract was as potent for
effective form against 8 species, the aqueous was likewise
2 of the species, less so for 3, and more so for 15 other
best against 8, while the quaternary and non-quaternary
Fall/Winter 2004 Journal of the American Herbalists Guild
J A H G
fall Winter book 05
1/2/05
2:16 pm
Page 34
34
were superior against 6 and 1, respectively, while the
with nutrient and tonic actions that can indirectly
berberine was best against only 1. The two native extracts
improve the body’s ability to respond to many different
performed better than the two fractions overall.
types of destructive stresses and challenges. Such indirect
Compared to the more complex extracts and fractions,
effects provide a supportive basis for the direct activities
berberine ranked last both for the number of species it was
for which each herb is specificly selected. In addition,
effective against and the number against which it was the
these direct activities may also be an expression of similar
most effective.
or dissimilar compounds with combined complementary
Synergy in living organisms can be due to at least two
types interactions. Pharmacodynamic synergy implies the
In thought and
action it should
effects, the usual understanding of therapeutic
synergism.
therapeutic effects of different constituents are combined,
Referring to the Ayurvedic medical tradition, the
while pharmacokinetic synergy involves increasing the
problem with acceptance of its complex approaches to
bioavailability of an active component. Both of these types
treatment by conventional scientific medicine is due to
of synergistic activities are described in a review article as
the limitations of standard medical research:
actually be our
involved in the therapeutic effects of three popular herbs
duty to think
used for their psychoactive influences (Spinella 2002). As
“People never ask what the active ingredient was in
an antidepressant, the hyperforin in St. John’s wort
the dinner they just consumed. … The active
(Hypericum perforatum) is a re-uptake inhibitor for
ingredient model does not stem from a strength of
serotonin, norepinephrine, and dopamine, while its
the scientific method, as often supposed; rather, it
concerning
hypericin,
drugs and their
monoamine
outside the
beaten path
action.
inhibit
stems from a weakness – from the inability of the
catechol-o-
reductionist method to deal with complex systems.
methyltransferase. Its procyanidin components increase
… Medical scientists must radically simplify the real
the water solubility of the hypericins.
world in order to examine it. A screening test for
flavonols,
oxidase
and/or
xanthones
(MAO)
and
Spinella also describes how the kava (Piper
anti-cancer agents, for instance, looks for cell death
methysticum) lactones kavain and dihydromethysticin act
in populations of malignant cells, whereas other
in an additive manner to inhibit calcium channels, and
mechanisms may function to rid the body of
this in turn potentiates the GABAergic activity of kava.
malignancies. Whole plant preparations have been
The combination of kava lactones causes a greater
found … to cause them [cancer cells] to differentiate
concentration of each in the brain than when they are
and return to normal healthy cells. … In establishing
given individually. In the case of valerian (Valeriana
a new medical paradigm, it will be no surprise if
officinalis), the aqueous extract stimulates sodium-
long-held biases are encountered.” (Sharma 1997)
dependent release of gamma aminobutyric acid (GABA),
while inhibiting its re-uptake. Other valerian extracts
As a consequence of the preference for the complete
enhance benzodiazepine binding at the GABA site, and
structures provided by the whole herb, those who rely on
its valerianic acid inhibits GABA breakdown. The
the traditional complex herb-based approaches now often
combined pharmacodynamic and pharmacokinetic
operate outside of the confines of limited scientific
effects of these herbs and their extracts magnify the
knowledge and, by extension, conventional practice. The
therapeutic influence of individual components.
limitations or lack of scientific investigations do not deter
In a broader sense synergism includes the systemic
them from reasonable use of herbal remedies based on
effects that may not directly affect the condition of
empirical observations. On the contrary, empirical
primary concern. Additional components in herbs with
knowledge helps refine the therapeutic choices. By
activities
metabolism,
incorporating both types of knowledge, clinical
elimination, anti-oxidant protection, immunity, and
applications can be enhanced. Lloyd expresses the
other functions contribute to overall systemic health and
advantage of utilizing empirical understanding thus:
that
enhance
digestion,
thereby help to establish a balanced physiological terrain.
J A H G
Many botanicals, especially in their most complex form
“Remedial agents there are, employed in confidence
as whole herbs, supply minor yet important components
by observing physicians, though the man of science
Journal of the American Herbalists Guild Fall/Winter 2004
fall Winter book 05
1/2/05
2:16 pm
Page 35
has not as yet fathomed the secret of their action.
therapeutic
Helpless is he [the scientist] to account for
counterproductive, when attempting to manage variations
approach
exclusively
risks
phenomena known to his microscope, his biological
in pathological expressions. Apparent pathology and
efforts are fruitless, chemistry fails. The empiricist
underlying predispositions both need to be effectively
accepts these facts, he continues to employ the agents
assessed and addressed, employing potency and/or subtly
discredited by all but those who, by repeated
when appropriate.
HISTORY & PHILOSOPHY
35
being
experiences, have learned their uses. With the object
of curing his patients, the observing physician walks
Adapted from Complex Herbs – Complete Medicines,
the forbidden path of an ostracized “irregular.””
2004, Eclectic Medical Publications, Sandy, OR
(Lloyd 1921)
Eclectics selected from available therapeutic measures
those that were most appropriate for individual patient
symptomatology, understood as specific indications. It is
with bold indifference to convention that, in so doing, the
utilization of botanical remedies was not only sustained by
the Eclectics, but further advanced:
“In thought and action it should actually be our duty
to think outside the beaten path concerning drugs
and their action. This, because vegetation is the sheet
anchor of our remedial agents. … Our materia
medica is not well known to practitioners of the
“Regular” school of medicine. … Should we accept
only that which has been recorded by or is known to
the majority of writers, it would be to confess that we
are devoid both of imagination, the motive power of
progress, and the right of thought creation, mental
speculation or practical research, outside the printed
page. To be Eclectic, we must be cosmopolitan, not
References
American Academy of Pediatrics Subcommittee on Anonymous
1910, Gross drugs versus active principles NY Med J.
[reprinted in 1910, Cal Ecl Med J. 3: 285-7]
Bhandari DK, Nath G, Ray AB, Tewari PV 2000, Antimicrobial
activity of crude extracts from Berberis asisatica stem bark
Pharmaceut Biol. 38(4):254-7
Lloyd JU 1905, Structural plant relationships Am J
Pharm.77:385-92
Lloyd JU 1909a, The debt we owe empiricism Cal Ecl Med J.
2:249-53 [reprinted in 1928 Ecl Med J. 88:251-4]
Lloyd JU 1909b, Apocynum (old domestic name, dog’s bane)
Ecl Med J. 69:454-6
Lloyd JU 1921, Empirical fallacies (and others) Am J Pharm.
93:627-32
Lloyd JU 1922, Infinities in pharmacy Ecl Med J. 82:326-36
Lloyd JU 1932a, Concerning chlorophyll Ecl Med J. 92:913;183-5
Lloyd JU 1932b, Natural products vs. separates Ecl Med J.
92:323-6
Sharma H 1997, Phytochemical synergism: beyond the active
ingredient module Alt Ther Clin Pract. pp. 91-6
Spinella M 2002, The importance of pharmacological synergy
in psychoactive herbal medicines. Alt Med Rev. 7:130-6
restricted.” (Lloyd 1932a)
Whereas 100 years ago the preference was for natural
complexity, the modern bias is for product uniformity
achieved by isolating components. Attempts at
standardizing botanical extract fractions to single
component content compromises both of these
approaches. Traditional methods of prescribing matched
the diversity of herbs and the complexity of their product
forms specifically to individual patients and their disease
expressions. Modern conventional protocols match
standard products and doses to specific diagnoses, so that
uniformity
is
extended
into
medical
practice.
Consequently, the complexity and diversity of individual
lives and patterns of symptomatology tend to be
minimized in standardized therapeutics. Using any single
Fall/Winter 2004 Journal of the American Herbalists Guild
J A H G